Tuesday, Jan 12, 2016

FDA Grants Priority Review for Venetoclax New Drug Application

  • Venetoclax, an investigational medicine, is a potential new way of treating the most common adult leukemia
  • Marketing Authorization Application validated by European Medicines Agency

South San Francisco, CA -- January 12, 2016 --


Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) and granted Priority Review for venetoclax for the treatment of people with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, including those with 17p deletion. Venetoclax is a small molecule inhibitor of the BCL-2 protein being developed in partnership with AbbVie, and was granted Breakthrough Therapy Designation by the FDA in April 2015 for the treatment of people with previously treated (relapsed or refractory) CLL with 17p deletion.

"Venetoclax is a potential new way to treat this difficult type of chronic lymphocytic leukemia,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We look forward to working with AbbVie and health authorities to bring this first-of-its-kind medicine to people who need more options."

A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases and to help ensure people have access to them through FDA approval as soon as possible. The NDA for venetoclax is based in part on data from the pivotal Phase II M13-982 study. A Marketing Authorization Application (MAA) has also been validated by the European Medicines Agency (EMA).

About Study M13-982
The NDA for venetoclax is based in part on data from the pivotal Phase II M13-982 study. M13-982 (NCT01889186) is a Phase II, open-label, single arm, multicenter study evaluating the efficacy and safety of venetoclax in patients with relapsed, refractory or previously untreated chronic lymphocytic leukemia (CLL) with 17p deletion. The study included 107 patients with relapsed or refractory disease, and all but one had 17p deletion. Additionally, about 50 patients with relapsed, refractory or previously untreated disease have been enrolled in the safety expansion cohort. The primary endpoint of the study is overall response rate (ORR) as determined by an independent review committee (IRC), and secondary endpoints include complete response (CR), partial response (PR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The level of minimal residual disease (MRD) in peripheral blood and/or bone marrow was assessed in a subset of patients.

Results from the study were recently presented at the 57th American Society of Hematology (ASH) Annual Meeting showing:

  • The study met its primary endpoint, with an ORR of 79.4 percent among the 107 patients with relapsed or refractory disease receiving venetoclax, as assessed by IRC. In addition, 7.5 percent of patients achieved a complete response with or without complete recovery of blood counts in the bone marrow (CR/CRi).
  • Forty-five patients had an assessment for MRD in the blood. Of these, 18 patients achieved MRD-negativity, meaning no cancer could be detected using a specific test. Ten of these 18 patients also had bone marrow assessments and six were MRD-negative.
  • At one year, 84.7 percent of all responses and 94.4 percent of MRD-negative responses were maintained. The one-year PFS and OS rates were 72 percent and 86.7 percent, respectively.
  • The most common serious adverse events were fever (7 percent), low red blood cell count as a result of immune response (7 percent), pneumonia (6 percent) and low white blood cell count with fever (5 percent). The most common Grade 3-4 adverse events were low white blood cell count (40 percent), low red blood cell count (18 percent) and low platelet count (15 percent). Grade 3 or higher infection occurred in 20 percent of patients. Laboratory tumor lysis syndrome was reported in five patients; none had clinical consequences.

About Venetoclax (RG7601, GDC-0199/ABT-199)
Venetoclax is an investigational small molecule designed to selectively bind and inhibit the BCL-2 protein, which plays an important role in a process called apoptosis (programmed cell death). It is believed that blocking BCL-2 may restore the signaling system that tells cells, including cancer cells, to self-destruct. The BCL-2 protein is linked to the development of resistance in certain blood cancers and is expressed in chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). In collaboration with AbbVie, venetoclax is being evaluated in a robust development program as a single agent or in combination with other medicines. There are ongoing Phase II and III studies for venetoclax in CLL, and Phase I and II studies are also ongoing in several other blood cancers, including indolent NHL, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and multiple myeloma (MM).

About Chronic Lymphocytic Leukemia (CLL)
CLL is one of the most common forms of blood cancer, and each year there are an estimated 5,000 deaths from CLL in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.
In certain cases of CLL, a part of chromosome 17 is lost and along with it an important gene that controls apoptosis (programmed cell death) called p53. The 17p deletion is found in 3 to 10 percent of previously untreated cases and approximately 30 to 50 percent of relapsed or refractory cases.

About Genentech In Hematology
For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines, Genentech’s pipeline of investigational hematology medicines includes an anti-PDL1 antibody (atezolizumab/MPDL3280A), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596), a small molecule antagonist of MDM2 (idasanutlin/RG7388) and in collaboration with AbbVie, a small molecule BCL-2 inhibitor (venetoclax/RG7601/GDC-0199/ABT-199). Genentech’s dedication to developing novel molecules in hematology expands beyond oncology, with the development of the investigational hemophilia A treatment emicizumab (ACE910).

About Genentech
Founded 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.